Myeloproliferative Neoplasms

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, conclude that the increasing complexity in myelofibrosis treatment options, including multiple JAK inhibitors and emerging combination therapies, signals an exciting era of individualized care, yet underscores the need for reevaluating study end points to enhance patient outcomes further.

Andrew Kuykendall, MD, emphasizes the importance of individualizing therapy for patients with myelofibrosis, focusing on improving quality of life and addressing specific issues like anemia and spleen volume, with the understanding that these treatments are palliative and goals should be revisited regularly.

The European Commission has expanded its approval of luspatercept to include frontline treatment of transfusion-dependent anemia due to lower-risk MDS.

Raajit K. Rampal, MD, PhD, discusses choosing among JAK inhibitors based on specific patient needs, such as platelet counts and anemia, emphasizing the importance of using the full dose for best efficacy and how different scenarios might influence the choice and sequencing of these drugs in practice.

Andrew Kuykendall, MD, discusses the efficacy and adverse effects of fedratinib, highlighting its potential in the second-line setting for patients resistant to ruxolitinib, with updates from FREEDOM-2 emphasizing manageable gastrointestinal tolerability concerns.

Patients with myeloproliferative neoplasms in accelerated or blast phase experience improved survival outcomes after hematopoietic cell transplantation.

Drs Rampal and Kuykendall highlight the benefits of pacritinib for patients with low platelet counts, as evidenced by the PERSIST-2 study, and momelotinib for patients with anemia, as shown in the MOMENTUM Phase 3 Study, focusing on their efficacy in spleen volume reduction and symptom relief in patients with myelofibrosis.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, reflect on the future of combination therapies in treating myelofibrosis, emphasizing the need to align study endpoints with treatment goals and highlighting the potential of various combinations based on promising preclinical and early phase study results.

Sunil Iyer, MD, expands on the impact of the FDA’s approval of luspatercept on the management of lower-risk myelodysplastic syndrome.

Joseph G. Jurcic, MD, highlights findings from the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM trials in myelofibrosis.

Joseph G. Jurcic, MD, discusses the benefits and limitations of several JAK inhibitors for patients with myelofibrosis.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss luspatercept with or without ruxolitinib for the treatment of anemia in patients with myelofibrosis. The combination has demonstrated promise in reducing transfusion dependency, as seen in data from ACE-536-MF-001, with ongoing phase 3 trials.

Andrew Kuykendall, MD, highlights the potential of selinexor plus ruxolitinib in JAK inhibitor-naïve patients with MF based on promising response rates in XPORT-MF-034 updated results, with plans for a phase 3 study. He also noted the need to manage nausea as a adverse effect.

In case you missed it, read a recap of every episode of OncLive On Air recorded in February 2024.

The FDA’s Oncologic Drugs Advisory Committee voted in favor of imetelstat for select patients with lower-risk myelodysplastic syndrome.

Raajit K. Rampal, MD, PhD, discusses promising data on navtemadlin plus ruxolitinib for patients with myelofibrosis who had suboptimal responses to ruxolitinib, showing significant improvements in spleen and symptom responses, with further phase 3 studies anticipated.

Andrew Kuykendall, MD, reviews data from TRANSFORM-1 on navitoclax plus ruxolitinib for untreated myelofibrosis, highlighting consistent response rates, no significant symptom improvement with the combination, and challenges managing thrombocytopenia caused by navitoclax, despite its activity and potential as a second-line treatment option.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss how the combination of the BET inhibitor pelabresib and the JAK inhibitor ruxolitinib led to greater reductions in spleen size and symptoms compared to ruxolitinib alone in JAK inhibitor-naïve patients with intermediate- or high-risk myelofibrosis in the MANIFEST and MANIFEST-2 trials, with an acceptable safety profile, providing evidence that targeting multiple inflammatory pathways could lead to better disease control.

Andrew Kuykendall, MD, and Raajit K. Rampal, MD, PhD, discuss how JAK inhibitors have reduced spleen size (splenomegaly) and constitutional symptoms like fatigue and fever in patients with myelofibrosis but that there is still room for improvement in treating other aspects of the disease like anemia and bone marrow fibrosis. They also share insights about the potential for combination therapies that target multiple pathways.

The National Comprehensive Cancer Network recommends ropeginterferon alfa-2b as first-line cytoreductive therapy for polycythemia vera.

Rusfertide displayed activity in phlebotomy-dependent polycythemia vera.

Bezuclastinib plus BSC improved mast cell burden and total symptom score vs placebo plus BSC in adult patients with nonadvanced systemic mastocytosis.

Luspatercept has been recommended for approval by the EMA for patients with transfusion-dependent anemia and lower-risk myelodysplastic syndromes.

David A. Sallman, MD, discusses the potential use of fedratinib to manage symptomatic myelodysplastic syndrome/myeloproliferative neoplasms.

Experts discuss how treatments, either monotherapy or combination, may impact the treatment landscape for MF and how they might choose among the new agents.